Right ventricular pacing reduces the rate of left ventricular relaxation and filling.

Right ventricular pacing alters left ventricular synchrony and loading conditions, each of which may independently influence left ventricular relaxation. Addition of a properly timed atrial contraction by using sequential atrioventricular (AV) pacing minimizes changes in left ventricular loading conditions, but ventricular asynchrony persists. To separate the effects of altered loading from those of asynchrony, the effects of right ventricular pacing and sequential AV pacing on the rate of isovolumic pressure decline (relaxation time constant), myocardial (segment) lengthening rate and chamber (minor axis dimension) filling rate were examined. In 12 open chest anesthetized dogs, left ventricular pressure (micromanometer) and either left ventricular free wall segment length transients (n = 6) or minor axis dimension transients (n = 6) were measured during right atrial, right ventricular and sequential AV pacing; length and dimension were measured using ultrasonic crystals. Compared with right atrial pacing, right ventricular pacing produced a decrease in systolic pressure, a reduction in fractional shortening, a prolongation of the relaxation time constant (23.5 +/- 0.7 to 29.8 +/- 0.8 ms, p less than 0.05), slower peak segment lengthening rate (6.2 +/- 0.6 to 4.6 +/- 0.8 s-1, p less than 0.05) and a slower rate of increase in chamber dimension (3.5 +/- 0.1 to 2.7 +/- 0.1 s-1, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Asynchronous (segmental early) relaxation of the left ventricle.

Segmental early relaxation, a form of left ventricular asynchrony, refers to lengthening of a myocardial segment before mitral valve opening. This phenomenon may occur in normal and diseased hearts; when it is seen in a diseased ventricle it may occur in either the abnormally contracting segment or the normal segment. Experimental data indicate that altered loading conditions, especially nonuniform distribution of load or functional inhomogeneities (as may occur with regional ischemia), or both, may result in asynchronous relaxation of the left ventricle.

Non-Q-wave myocardial infarction following thrombolytic therapy: a comparison of outcomes in patients randomized to invasive or conservative post-infarct assessment strategies in the Veterans Affairs non-Q-wave Infarction Strategies In-Hospital (VANQWISH) Trial.

OBJECTIVES: We wished to determine the effect of post-infarct management strategy on event rates (death or recurrent nonfatal myocardial infarction [MI]) in patients who evolved non-Q-wave MI (NQMI) following thrombolytic therapy. BACKGROUND: Patients who evolve NQMI following thrombolytic therapy are often considered to be at high risk and are frequently managed with routine early invasive testing despite a lack of data supporting improved outcome. METHODS: The Veterans Affairs Non-Q-Wave Infarction Strategies In-Hospital (VANQWISH) study included 115 patients who evolved NQMI following thrombolytic therapy. We compared the event rates in patients randomized to routine early coronary angiography with those in patients randomized to a conservative strategy of noninvasive functional assessment, with angiography reserved for patients with spontaneous or induced ischemia. RESULTS: During an average follow-up of 23 months, 19 of 58 patients (33%) randomized to the invasive management strategy died or suffered recurrent nonfatal MI, compared with 11 of 57 patients (19%) randomized to the conservative strategy (p = 0.152). Equivalent numbers of patients were subjected to revascularization (percutaneous transluminal coronary angioplasty or coronary artery bypass graft). There were more deaths in the invasive management group than in the conservative management group (11 vs. 2). Excess deaths could not be attributed to periprocedural mortality. CONCLUSIONS: Overall event rates (death or recurrent nonfatal MI) are comparable with conservative and invasive strategies in patients who evolve NQMI following thrombolytic therapy. Mortality rate in patients managed conservatively is low (3.5%), and routine invasive management may be associated with an increased risk of death.

Mechanisms of pulsus paradoxus during resistive respiratory loading and asthma.

To determine the mechanisms of pulsus paradoxus during asthma, six subjects known to have cold air bronchial hyperreactivity were studied while in a quiescent phase of their disease. All were free of significant airway obstruction at the time of study. After placement of an esophageal balloon to estimate intrathoracic pressure, the subjects were assessed during quiet breathing, resistive airway loading and then during a stable period of airway obstruction induced by cold air. Steady state left ventricular volume and performance were measured using radionuclide ventriculography; right ventricular volume was calculated from the stroke volume ratio and right ventricular ejection fraction. Cardiac cycles were segregated according to their occurrence in inspiration or expiration using a flow signal from a pneumotachograph. Combined inspiratory and expiratory resistance produced pulsus paradoxus and changes in esophageal pressure that were similar to those during asthma and significantly greater than those during quiet breathing. These changes were accompanied by decreases in left ventricular diastolic volume and stroke volume during inspiration, and increases in these variables during expiration; right ventricular volume and stroke volume demonstrated changes reciprocal to those seen in the left ventricle. These data indicate that during periods of increase in airway resistance, abnormal pulsus paradoxus results from an exaggeration in the normal inspiratory-expiratory difference in stroke volume mediated primarily by the effects of intrathoracic pressure on ventricular preload.

Design and baseline characteristics of the Veterans Affairs Non-Q-Wave Infarction Strategies In-Hospital (VANQWISH) trial. VANQWISH Trial Research Investigators.

OBJECTIVES: The Veterans Affairs Non-Q-Wave Infarction Strategies In-Hospital (VANQWISH) trial was designed to compare outcomes of patients with a non-Q wave myocardial infarction (NQMI) who were randomized prospectively to an early "invasive" strategy versus an early "conservative" strategy. The primary objective was to compare early and late outcomes between the two strategies using a combined trial end point (all-cause mortality or nonfatal infarction) during at least 1 year of follow-up. BACKGROUND: Because of the widely held view that survivors of NQMI are at high risk for subsequent cardiac events, management of these patients has become more aggressive during the last decade. There is a paucity of data from controlled trials to support such an approach, however. METHODS: Appropriate patients with a new NQMI were randomized to an early "invasive" strategy (routine coronary angiography followed by myocardial revascularization, if feasible) versus an early "conservative" strategy (noninvasive, predischarge stress testing with planar thallium scintigraphy and radionuclide ventriculography), where the use of coronary angiography and myocardial revascularization was guided by the development of ischemia (clinical course or results of noninvasive tests, or both). RESULTS: A total of 920 patients were randomized (mean follow-up 23 months, range 12 to 44). The mean patient age was 61 +/- 10 years; 97% were male; 38% had ST segment depression at study entry; 30% had an anterior NQMI; 54% were hypertensive; 26% had diabetes requiring insulin; 43% were current smokers; 43% had a previous acute myocardial infarction; and 45% had antecedent angina within 3 weeks of the index NQMI. CONCLUSIONS: Baseline characteristics were compatible with a moderate to high risk group of patients with an NQMI.

Effect of propranolol on the left ventricular response to the Valsalva maneuver in normal subjects.

Ten normal subjects performed the Valsalva maneuver before and after the administration of propranolol (1 mg/kg). Changes in left ventricular (LV) size and function were assessed with noninvasive techniques (echocardiography and sphygmomanometer). Data were obtained at baseline, at 20 seconds of the strain phase (phase II) and 10 seconds after the release of strain (phase IV). In the control state (before propranolol), blood pressure decreased during phase II and exceeded baseline after the release of strain ("overshoot") in phase IV; after the administration of propranolol, the pressure overshoot characteristic of phase IV was no longer present. End-diastolic dimension decreased during the strain phase, but returned to baseline values during recovery in both control and propranolol states. LV stress-dimension and stress-shortening relations before and after propranolol indicate that an increase in LV contractility beginning during phase II and extending into phase IV was attenuated after propranolol. Although the absence of phase IV blood pressure overshoot may be clinically useful in identifying patients with impaired left ventricular function, beta-adrenergic receptor blocking agents can also produce this hemodynamic response in the presence of normal ventricular function.

Implications of increased myocardial isoenzyme level in the presence of normal serum creatine kinase activity.

Although increased serum creatine kinase (CK) activity in the presence of an increased level of myocardial-specific isoenzymes (CKMB) has been strongly associated with acute myocardial infarction, the significance of an increased serum CKMB level in the presence of a normal total CK level is uncertain. In 335 consecutive patients suspected of having an acute myocardial infarction and 71 control subjects, peak serum CKMB and CK levels were correlated with the presence of other clinical criteria for acute myocardial infarction: (1) typical chest pain, (2) increased myocardial lactate dehydrogenase (LDH1/LDH2), (3) acute electrocardiographic changes (new or ST-T wave changes with evolution), and (4) an elevated CKMB level on 2 or more determinations or a typical CK curve. No control subject had an increase in CK or CKMB or any of the 4 criteria for myocardial infarction. Of the 176 subjects with normal CK and normal CKMB (Group 1), only 11% had more than a single criterion, and none had more than 2 criteria consistent with myocardial injury. In contrast, of the 83 with elevated CK and CKMB levels (Group 2), 93% had 2 or more and 81% had 3 or more of the 4 criteria. Of the 63 patients with elevated CKMB but a persistently normal CK (Group 3), 65% had 2 or more criteria for acute myocardial infarction and 77% had subendocardial electrocardiographic changes; these patients resembled those with both elevated CK and MB. The phenomenon of elevated CKMB with normal CK occurred in 20% of the patients aged greater than or equal to 70 years but in only 10% of the younger group (p less than 0.01). These findings suggest that elevated CKMB with normal CK likely represents definite myocardial injury, is more likely represents definite myocardial injury, is more common in the elderly, and should be considered part of the spectrum of nontransmural myocardial infarction.

Adjunctive nifedipine therapy in high-risk, medically refractory, unstable angina pectoris.

Patients with unstable angina pectoris who remain symptomatic at rest after hospitalization are at increased risk of death or myocardial infarction. This report presents the results of adding the calcium influx blocking agent nifedipine to aggressive therapy with nitrates and beta-blocking drugs in 47 hospitalized patients. The patients were followed up for an average of 12 months. Twenty-two (47%) improved sufficiently to be discharged; despite this symptomatic improvement, 8 had cardiac events within 4 months. Eighteen patients had no symptomatic improvement and 7 of them had cardiac events in 4 months. In 7 others, relief was insufficient to permit discharge, and 1 of these patients had myocardial infarction. In all, 31 patients were treated with medical therapy only. Twenty-one of these patients had a favorable short-term response to nifedipine; 13 died or had an infarction in less than 4 months. Two of 16 patients who underwent coronary artery bypass surgery had cardiac events. The presence of electrocardiographic changes with pain did not identify either a group at higher risk or a group with a better outcome with nifedipine. We conclude that in a high-risk subset of patients with unstable angina pectoris, nifedipine does not reduce morbidity or mortality or the need for bypass surgery, but relieves symptoms in many patients. An early symptomatic response to nifedipine did not predict a reduced incidence of subsequent cardiac events.

Left ventricular dysfunction in deteriorating patients with chronic obstructive pulmonary disease.

OBJECTIVE: To evaluate the effectiveness of simple clinical variables and radionuclide ventriculogram in separating those patients with isolated chronic obstructive pulmonary disease (COPD) from those with COPD and coexisting left ventricular dysfunction (LVD). DESIGN: Retrospective record review of 77 patients with increasing dyspnea, defined as recent deterioration in exercise tolerance, new use of corticosteroids, or recent hospital admission for COPD; referred to the outpatient Pulmonary Rehabilitation Program at the Cincinnati Veterans Affairs Medical Center from July 1987 to October 1992. SETTING: Outpatient medical clinic. PATIENTS: Veterans who were referred to the Pulmonary Rehabilitation Program. MEASUREMENTS: History and physical findings, pulmonary function tests, arterial blood gases, distance achieved in a 12-min walk, dyspnea score, electrocardiogram, chest radiograph, and radionuclide multigated ventriculography. RESULTS: Twenty-five of 77 patients evaluated in the Pulmonary Rehabilitation Program for increasing dyspnea were functionally more limited (12-min walk 10.4 vs 13.9 laps; MRC score 2.68 vs 2.06; p < 0.05) and had left ventricular dysfunction (LVD) (left ventricular ejection fraction < 40%) associated with wall motion abnormalities on radionuclide ventriculogram. Careful standard clinical evaluation did not separate those patients with COPD from those with both COPD and LVD. CONCLUSIONS: LVD was found in 32% of patients with COPD presenting with symptomatic deterioration. Since the therapeutic approach to these two disorders differs, the identification of patients with LVD is important. Prospective studies are needed to identify the most cost-effective approach to this problem of coexisting disease and to evaluate the benefit from therapy.

Preoperative and perioperative management of cardiac patients undergoing noncardiac surgery.

Cardiac diseases, particularly coronary artery disease and its risk factors, are associated with the majority of perioperative complications in patients undergoing major noncardiac surgery. Risks are remarkably low overall, yet for selected patients undergoing high-risk procedures, the chances of complications remain reasonably high. The literature has focused largely on identifying patients in whom complications are most likely to occur, using clinical assessment, including RFI, specialized cardiac testing, and perioperative monitoring. Characteristics of the patient and the surgery both influence outcomes. Current practices may have swung toward excessive testing, especially in patients whose surgical risks are low or moderate. Surprisingly little attention has been devoted to the evaluation of preoperative interventions for reducing perioperative risk. Some observations support the feasibility of performing noncardiac surgery in some high-risk groups using support devices or temporizing techniques. The general application of percutaneous or surgical revascularization as a means of reducing perioperative risk has not been assessed and to date represents an expensive and perhaps risky strategy. In patients who satisfy the usual symptomatic or prognostic criteria for coronary revascularization, its timing should depend on the urgency and risk of the noncardiac procedure. Finally, patients with cardiac devices--pacemakers, prosthetic valves, implantable debrillators, and antitachycardia devices--and survivors of congenital and transplant surgery have specific needs that require careful attention, going beyond the usual vigilance required in the perioperative period.

Indications for and timing of surgical intervention in infective endocarditis.

Infective endocarditis, especially when it involves prosthetic valves, is a serious, often fatal illness. Although antibiotics are essential in management, surgery is required in many patients who develop even incipient heart failure and structural complications. Early identification and referral results in improved mortality and morbidity rates, and there is evidence that surgery should play a larger role in managing infective endocarditis. Patients with intracardiac pacemakers and cardioverting devices represent a growing reservoir of patients with the potential to develop endocarditis.

Tricuspid valve disease. Clinical evaluation, physiopathology, and management.

The tricuspid and mitral valves are homologous whose function depends on coordination among components. Isolated tricuspid valve abnormalities are relatively uncommon. Rheumatic disease, chemicals, immunologic and degenerative disorders alter leaflet anatomy and may result in either stenosis, insufficiency or a combination. More often, tricuspid disorders present as a component of congenital syndromes or secondary to pulmonary vascular or let heart disease which alter geometry and function of nonleaflet components.

Myocardial relaxation. VI. Effects of beta-adrenergic tone and asynchrony on LV relaxation rate.

We studied the effect of left ventricular (LV) asynchrony and alterations in beta-adrenergic tone on the systolic load (pressure) dependency of LV isovolumic relaxation rate in anesthetized dogs. The time constant (T) of isovolumic exponential pressure decline was used as an index of relaxation rate. Variably afterloaded LV contractions resulted in a progressive increase in LV end-systolic pressure from 124 +/- 6 in the control beat to 176 +/- 11 mmHg in the third beat and a progressive lengthening of T from 19 +/- 2 to 30 +/- 4 ms. The direct relation between LV end-systolic pressure and T was nearly linear (r = 0.98), and the slope (k) of this relation was taken to reflect the systolic load dependency of T. Administration of isoproterenol (n = 6) produced a decrease in k from 0.11 +/- 0.02 to 0.08 +/- 0.02 (P less than 0.05); with propranolol (n = 6), k increased from 0.08 +/- 0.02 to 0.27 +/- 0.04 (P less than 0.01). Right ventricular epicardial pacing (n = 6) produced an asynchronous LV contraction and an increase in k from 0.09 +/- 0.02 (atrial pacing) to 0.25 +/- 0.04 (P less than 0.01). These studies confirm the dependency of LV relaxation rate on systolic loads and indicate that this form of load-dependent relaxation can be modified by alterations in beta-adrenergic tone and LV asynchrony. The observed alterations suggest the importance of temporal dispersion of the contraction-relaxation sequence as a mechanism responsible for disturbed relaxation.

Myocardial relaxation. III. Reoxygenation mechanics in the intact dog heart.

Reoxygenation of hypoxic isolated cardiac muscle results in prolonged duration of contraction-relaxation. To determine whether similar mechanical changes occur in the intact left ventricle (LV), and especially to assess the influence of prolonged relaxation on LV diastolic stiffness, we examined LV pressure transients (micromanometer) and changes in myocardial segment length (ultrasonic transit time) during reoxygenation in 22 anesthetized dogs following 15 minutes of hypoxia (PaO2 = 21 +/- 2 mm Hg). The time constant (T) of LV isovolumic exponential pressure decline was used as an index of myocardial relaxation; LV end-diastolic stiffness was assessed from stiffness constants derived from multiple coordinates of end-diastolic pressure and segment length (volume loading). During reoxygenation, after LV systolic pressure and segment length measurements had returned to control levels, relaxation was prolonged; T increased from a control of 32 +/- 2 to 44 +/- 3 msec at 5 minutes of reoxygenation (P less than 0.01). Prolonged relaxation resulted in a consistent increase in LV early-diastolic pressures. Furthermore, calculated values for LV end-diastolic stiffness increased during reoxygenation when the next beat began less than 3.5 T after maximum negative dP/dt; this condition was present more frequently at a heart rate of 150 beats/min than at 120 beats/min. Thus, rapid correction of acute hypoxia in the dog results in prolonged LV relaxation; prolonged relaxation can influence LV end-diastolic stiffness when relaxation is sufficiently slow and/or when diastole is sufficiently short.

The effect of acute alterations in left ventricular afterload and beta-adrenergic tone on indices of early diastolic filling rate.

The effects of an acute increase in left ventricular systolic pressure and the effects of an intravenous isoproterenol infusion on myocardial (segment) lengthening rate and chamber (minor axis dimension) filling rate were examined in 12 anesthetized dogs. Measurements of left ventricular systolic pressure (by micromanometer) and of segment length and chamber dimension transients (by ultrasonic crystals) were made in variably afterloaded beats (three-beat descending aortic cross-clamp) before and during an isoproterenol infusion that raised (+)dP/dt by 40%. During the baseline state, we found an inverse relation between the peak rate of increase in minor axis dimension [(+)dD/dt] and systolic pressure over a wide range of systolic pressures (110-160 mm Hg) and end-systolic dimensions (25-40 mm); peak (+)dD/dt and end-systolic dimension were also inversely related. During isoproterenol infusion, end-systolic dimension fell from 29.7 +/- 3.1 to 28.0 +/- 3.1 mm and (+)dD/dt increased from 79.6 +/- 8.0 to 90.1 +/- 8.7 mm/sec; however, the slope and y intercept of the relation between (+)dD/dt and end-systolic dimension were unchanged. Peak (+)dD/dt at a common end-systolic dimension of 31 mm was nearly equal during baseline and isoproterenol states (64.2 +/- 6.3 vs. 65.1 +/- 6.6 mm/sec). Similar results were found using segment length transients. We interpret these data to indicate that (+)dD/dt is strongly influenced by changes in systolic pressure and dimension and that isoproterenol-induced changes in (+)dD/dt are mediated, at least in part, through changes in systolic pressure and dimension.

Comparison of contractile state and myosin isozymes of rat right and left ventricular myocardium.

We compared myocardial mechanics and myosin isozymes of right and left ventricular papillary muscles from adult (6 to 8 month old) male rats. Analysis of force velocity relations indicate that right ventricular papillary muscles contract more rapidly than left at light loads (2.68 +/- 0.13 vs 2.18 +/- 0.07 muscle lengths/s measured 75 ms following stimulation, at 0.5 g/mm2; P less than 0.01). Right ventricular papillary muscles had significantly more of the alpha heavy chain containing V1 myosin isozyme and less of the V3 containing beta heavy chain myosin isozyme than left ventricular preparations (P less than 0.05). Papillary muscle and ventricular free wall myosin isozyme distribution were not significantly different within their respective chambers. The presence of a relatively larger proportion of the alpha heavy chain containing myosin isozyme (V1) in right ventricle papillary muscles relative to left correlated with the more rapid velocities of shortening seen in right ventricular papillary muscles (r = 0.60; P less than 0.01).

Serial effects on left ventricular load and contractility during hemodialysis in patients with concentric hypertrophy.

To separate the effects of hemodialysis on loading conditions from those on contractile state, six patients with concentric left ventricular hypertrophy and normal left ventricular function were studied before, during, and after hemodialysis. Two-dimensional-directed M-mode ultrasound was used to measure left ventricular dimensions and wall thickness; a sphygmomanometer and carotid pulse recording were used to determine peak and end-systolic blood pressure. From these data, meridional stress at end systole was calculated and stress-dimension and stress-shortening relations were derived; measurements of metabolic parameters were made simultaneously. Heart rate and systolic blood pressure were stable throughout dialysis. Reductions in left ventricular dimensions and increased shortening were evident by 30 minutes of dialysis and were largely complete by mid-dialysis. These changes coincided with a decrease in potassium and an increase in ionized calcium but not in pH, which changed only in the latter half of dialysis. When stress-dimension and stress-shortening relations were examined, both individual and group data for all coordinates before, during, and after dialysis demonstrated an excellent linear fit consistent with a single contractile state. We conclude that in stable patients with left ventricular hypertrophy, the reduction in heart size and improvement in shortening are due primarily to reductions in preload and afterload.

Myocardial relaxation: effects of preload on the time course of isovolumetric relaxation.

We studied the effect of an isolated increase in preload on isovolumetric relaxation in the intact dog heart and isometric relaxation in isolated cardiac muscle (dog and rat) preparations. In eight anesthetized dogs, 8 to 12 ml of blood was infused into the left ventricle during a single diastole. The exponential time constant (T) of isovolumetric relaxation was measured in single-beat experiments in which the left ventricular systolic pressure increased (112 +/- 2 to 128 +/- 3 mm Hg; p less than .05, n = 62). In a second series of experiments, left ventricular systolic pressure was held constant (109 +/- 2 to 107 +/- 2 mm Hg; p = NS, n = 23) by simultaneous ventricular infusion and aortic unloading. In the first protocol, T increased from 28.0 +/- 0.4 to 30.7 +/- 0.4 msec (p less than .05), whereas in the second protocol (constant systolic pressure) there was no change in T. The time course of isometric relaxation was also studied in six rat left ventricular papillary muscles and four dog right ventricular trabecular muscles. Preload was varied from 30% to 100% of the peak of the isometric length-tension curve in each muscle. Over this wide range of preload, the isometric force decline recordings were superimposable as long as the comparisons were made at equal levels of total load. Thus an isolated increase in preload does not influence the time course of isovolumetric relaxation.

Influence of exogenously generated oxidant species on myocardial function.

Oxygen-derived free radicals (OFR) have been implicated as mediators of tissue injury in various disease states. Their participation in myocardial injury due to ischemia-reperfusion has also been suggested. To characterize the mechanical dysfunction associated with OFR-induced injury, we studied alterations in isometric contractions of rat papillary muscle at 28 degrees C. A purine-xanthine oxidase system was used to generate OFR. Neither purine nor xanthine oxidase alone had significant effects on rest or active tension, duration of the contraction, or peak rates of tension development or decline. In contrast, their combination resulted in a reduction of active tension to 38% of base-line values without alteration in rest tension. This reduction was largely due to a decline in the peak rate of tension development. When catalase or superoxide dismutase was introduced into the bath prior to the generation of OFR, catalase but not superoxide dismutase offered essentially complete functional protection. These results substantiate that impaired myocardial function can result from exposure to OFR. In this case the active radicals appear to be either peroxides or hydroxyl and not superoxide. These observations provide a basis for understanding the functional protection afforded ischemic myocardium by OFR scavenging enzymes.